Targeted DNase treatment of obstructive lung disease: a pilot randomised controlled trial DOI Creative Commons
Netsanet A. Negewo, Natalie M. Niessen,

Penelope J. Baines

и другие.

ERJ Open Research, Год журнала: 2024, Номер 11(1), С. 00347 - 2024

Опубликована: Окт. 10, 2024

Sputum extracellular DNA (eDNA) is associated with disease severity in asthma and COPD therefore emerging as a potential therapeutic target. The aim of this study was to investigate the effect 10 days recombinant human DNase (rhDNase) treatment eDNA-high on sputum eDNA levels, neutrophil-related inflammation, lung function symptoms. Adults (n=80) or (n=66) were screened for presence high (>20 µg·mL-1) those eligible (n=18 asthma, n=17 COPD) randomised two-period crossover controlled trial consisting daily nebulised rhDNase (2.5 mg/2.5 mL) placebo (5 mL 0.9% saline) days, 2-week washout period. primary outcome eDNA, secondary outcomes included neutrophil trap (NET)-related biomarkers, inflammatory cell counts, respiratory At screening, significantly higher total count, colour score inflammation (HNP1-3, LL-37 interleukin-1β) both compared low groups. In participants older had poorer control eDNA. Administration reduced levels (median (Q1-Q3) Pre: 48.4 (22.1-74.1); Post: 17.0 (5.0-31.0) µg·mL-1; p=0.022) 39.3 (36.7-55.6); 25.4 (11.3-38.6) p=0.044) placebo. Symptoms, NET biomarkers remained unchanged. there reduction banded blood neutrophils (3.2 (0-7.7) 0.0 (0.0-1.5); p=0.044). Targeted effectively COPD.

Язык: Английский

What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study DOI Creative Commons
Cristina Diego, Ana Lasierra,

Lucía López-Vergara

и другие.

Respiratory Research, Год журнала: 2024, Номер 25(1)

Опубликована: Янв. 19, 2024

Abstract Background Neutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, are scarce data evolution during the disease. We studied circulating NET markers in patients with throughout hospitalization. Methods prospectively included 93 (201 blood samples), evaluating disease 3 evolutionary phases (viral, early, late inflammation). Of these, 72 had 180 samples various phases. also evaluated 55 controls similar age, sex comorbidities. measured 4 serum: cfDNA, CitH3, MPO-DNA NE-DNA complexes; as well neutrophil-related cytokines IL-8 G-CSF. Results The group higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), MPO-DNA, (7.87 2.56 ng/mL; 0.80 0.52 1.04 0.72, respectively, < 0.001 for all) than hospitalisation. cfDNA was only marker clearly severity, it remained non-survivors Only an independent risk factor mortality need intensive care. count, IL-8, G-CSF were significantly severity. showed significant correlations (r: 0.483, 0.001), including all across grades, they days 10–16 of those who died. Correlations among other lower expected. Conclusions biomarkers NETs present associated mortality, but three little or association these outcomes. activity neutrophil count better reflected formation. appeared be more overall tissue damage; previous widespread use this could overestimated relationship between Currently, limitations accurate measurement that make difficult assess its true role pathogenesis.

Язык: Английский

Процитировано

8

A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury DOI Open Access
Xinyu Zhou,

Jiajia Jin,

Tangfeng Lv

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1464 - 1464

Опубликована: Янв. 25, 2024

Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation treatment of ARDS remains major research focus. There are various causes ARDS, among which pneumonia non-pulmonary sepsis most common. Trauma blood transfusion can also cause ARDS. In aggregation infiltration neutrophils in lungs have great influence on development disease. Neutrophils regulate inflammatory responses through pathways, release neutrophil extracellular traps (NETs) is considered to be one important mechanisms. NETs mainly composed DNA, histones, granuloproteins, all mediate downstream signaling pathways that activate responses, generate immune clots, damage surrounding tissues. At same time, components promote formation NETs, thus forming vicious cycle continuously aggravates progression associated with cytokine storms balance. Since DNA main component DNase I viable drug for removing NETs. Other therapeutic methods inhibit worthy further exploration. This review discusses mechanism Understanding association between may help develop new perspectives

Язык: Английский

Процитировано

6

Neutrophil Extracellular Traps and Respiratory Disease DOI Open Access
Paul T. King,

Lovisa Dousha

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(8), С. 2390 - 2390

Опубликована: Апрель 19, 2024

Extracellular traps made by neutrophils (NETs) and other leukocytes such as macrophages eosinophils have a key role in the initial immune response to infection but are highly inflammatory may contribute tissue damage. They particularly relevant lung disease, with pulmonary anatomy facilitating their ability fully extend into airways/alveolar space. There has been rapid expansion number of published studies demonstrating variety important respiratory diseases including chronic obstructive cystic fibrosis, bronchiectasis, asthma, pneumonia, COVID-19, rhinosinusitis, interstitial disease cancer. The expression NETs is specific process, diagnostic tests need differentiate them from pathways/causes cell death that also characterised presence extracellular DNA. targeting this pathway therapeutics significant clinical benefit; however, current trials/evidence at very early stage. This review will provide broad overview possible treatment disease.

Язык: Английский

Процитировано

6

Involucrasin B suppresses airway inflammation in obese asthma by inhibiting the TLR4-NF-κB-NLRP3 pathway DOI
Zhu‐Ya Yang, Xiaohong Li,

Lisha Wei

и другие.

Phytomedicine, Год журнала: 2024, Номер 132, С. 155850 - 155850

Опубликована: Июль 2, 2024

Язык: Английский

Процитировано

6

Molecular mechanism of Jianpiyifei II granules in the treatment of chronic obstructive pulmonary disease: Network pharmacology analysis, molecular docking, and experimental assessment DOI
Dan Xie, Jingyu Quan, Xuhua Yu

и другие.

Phytomedicine, Год журнала: 2024, Номер 126, С. 155273 - 155273

Опубликована: Янв. 6, 2024

Язык: Английский

Процитировано

5

Pseudomonas aeruginosa in chronic lung disease: untangling the dysregulated host immune response DOI Creative Commons

Rhea Nickerson,

Christina S. Thornton, Brent Johnston

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июнь 28, 2024

is a highly adaptable opportunistic pathogen capable of exploiting barriers and immune defects to cause chronic lung infections in conditions such as cystic fibrosis. In these contexts, host responses are ineffective at clearing persistent bacterial infection, instead driving cycle inflammatory damage. This review outlines key components the response

Язык: Английский

Процитировано

5

PRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury DOI Creative Commons
Xinyue Du, Baiyang Ren, Chang Li

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 29, 2024

Abstract Excessive host immune responses contribute to severe malaria with high mortality. Here, we show that PRL2 in innate cells is highly related experimental disease progression, especially the development of murine malaria. In absence myeloid cells, Plasmodium berghei infection results augmented lung injury, leading significantly increased Intravital imaging revealed greater neutrophilic inflammation and NET formation lungs conditional knockout mice. Depletion neutrophils prior onset protected mice from NETs associated eliminated difference between WT CKO regulates neutrophil activation accumulation via Rac-ROS pathway, thus contributing ALI. Hydroxychloroquine, an inhibitor degradation alleviates tissue damage vivo. Our findings suggest serves as indicator progression addition, our study indicated importance injury. It might open a promising path for adjunctive treatment NET-associated disease.

Язык: Английский

Процитировано

4

Identification of potential targets regulating neutrophil extracellular traps in acute rejection of kidney transplantation based on transcriptomics and animal experiments DOI
Jun Pei,

Huali Weng,

Jinpu Peng

и другие.

International Immunopharmacology, Год журнала: 2025, Номер 147, С. 114008 - 114008

Опубликована: Янв. 5, 2025

Язык: Английский

Процитировано

0

The Diagnostic Value of Plasma NETs Levels and iCEB in Silent Myocardial Ischemia in Maintenance Hemodialysis Patients DOI Creative Commons
Haifei Liu,

Jun-Ling Han,

Wei‐Jie Ni

и другие.

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 847 - 862

Опубликована: Янв. 1, 2025

This study evaluated the diagnostic value of plasma Neutrophil extracellular traps (NETs) levels and index cardiac electrophysiological balance (iCEB) in identifying silent myocardial ischemia (SMI) maintenance hemodialysis (MHD) patients. cross-sectional observational involved patients receiving MHD treatment. Data were collected on coronary angiography performed our hospital from February 2023 to 2024. Patients diagnosed with via but without obvious symptoms grouped as SMI group, while those control group. Plasma NETs assessed using markers indicative components including double-stranded DNA (dsDNA), circulating free (cfDNA) myeloperoxidase, iCEB (QT/QRS) electrocardiographic findings obtained. Additionally, echocardiographic parameters, inflammatory markers, biomarkers analyzed. Receiver operating characteristic (ROC) analysis employed evaluate accuracy SMI. A total 114 included, 79 participants group 35 The exhibited significantly elevated associated (dsDNA(37.89±4.55 vs 31.64±5.32, P<0.001), cfDNA(11.27±2.03 8.91±1.84, MPO-DNA(23.69±4.01 17.52±3.41, P<0.001)), well higher compared group(56.45±7.67 45.89±6.23, P<0.001). Furthermore, electrocardiography findings, showed significant differences between two groups. ROC demonstrated potential accuracies iCEB, an area under curve (AUC) 0.908, sensitivity 0.987, specificity 0.829 for highlights combined patients, providing valuable insights into early detection risk stratification strategies this population.

Язык: Английский

Процитировано

0

The role of neutrophil response in lung damage and post-tuberculosis lung disease: a translational narrative review DOI Creative Commons
Ana Paula Santos, Luciana Silva Rodrigues, Nils Rother

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 7, 2025

It is estimated that more than 150 million individuals alive in 2020 had survived tuberculosis (TB). A portion of this large population continues to experience chronic respiratory abnormalities, with or without symptoms, due previous active pulmonary TB. This condition known as Post-TB Lung Disease (PTLD), involves a complex interaction between pathogen, host and environmental factors. These interactions are believed drive hyperinflammatory process the lungs during TB, resulting tissue damage, which may lead radiological sequelae, impaired function, clinical such cough, dyspnea, hemoptysis, infections. Such complications impose significant health, financial, social burdens, remain poorly understood inadequately addressed by health care systems. Given heterogeneity immune cells their products infiltrating airways lung parenchyma acute inflammation caused Mycobacterium infection, it evident TB immunopathology multifactorial. Among various components involved, neutrophils have recently emerged critical contributors deleterious response against leading severe damage. In translational narrative review, we aim summarize role primary - proteases (such elastase), matrix metalloproteinases extracellular traps (NETs) We highlight new concepts emerging evidence neutrophil involvement disease, translating these insights from "bench bedside" facilitate dialogue fundamental researchers practitioners. Additionally, present potential targets for future treatment strategies could mitigate even prevent PTLD.

Язык: Английский

Процитировано

0